This is a single center, phase 1, randomized, double-blind, placebo-controlled sequential study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of ISM8969 in healthy adults and elderly participants and obese adult participants at risk of cardiovascular disease.

Inclusion Criteria:

Participants must meet all the following criteria to be included in the study:

Inclusion criteria 1~4 are only for the healthy participants in the SAD and MAD study:

1. Male or female participants, including adult participants (≥18 and <65 years of age) for the SAD cohorts 1-6 and MAD cohorts 1-3, and elderly participants (≥65 and ≤80 years of age) for MAD cohort 4.

2. Body mass index (BMI) >18.5 and <30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.

3. Non-smokers (no use of tobacco or nicotine products within 1 month prior to screening).

4. Healthy as defined the current protocol.

   Inclusion criteria 5~9 are only for the obese participants at risk of cardiovascular disease in MAD study):

5. Male or female, ≥18 and ≤65 years of age.

6. 30.0 kg/m2 ≤ BMI < 42.0 kg/m2.

7. No change in body weight or self-reported change of less than 5.0% within 3 months before screening.

8. Presence of 1 or more risk factors for cardiovascular disease such as hypertension, hyperlipidemia. If present, must be controlled with stable medication dose/therapy (defined as a stable medication dose/therapy for 3 months or longer).

9. hsCRP ≥3 mg/L.

Exclusion Criteria:

Participants for whom any of the following applies will be excluded from the study:

1. Columbia suicide severity rating scale (C-SSRS) score above Type 1 ideation.
2. Positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen and antibody, treponema pallidum antibody or QuantiFERON®-TB test at screening.
3. Positive pregnancy test or lactating female participant.
4. History of any central nervous system (CNS) disorder or history of seizure of any cause.
5. Clinically significant 12-lead ECG, physical examination, vital signs or laboratory abnormalities at screening, including but not limited to defined in the protocol.
6. History of significant cardiovascular or cerebrovascular disease within 6 months before screening, including but not limited to defined in the protocol.
7. History of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, or in situ carcinomas of the cervix) for less than 5 years; or there is a potential malignancy during screening.
8. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days (or 5 half-lives, whichever is longer) prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days (or 5 half-lives, whichever is longer) prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
9. Presence of contraindication to lumbar puncture or lumbar catheter as judged by Investigator.